Identification of potent and selective TACE inhibitors via the S1 pocket

By focusing on the P1 portion of the piperidine beta-sulfone ligands we identified a motif that induces selectivity and resulted in a series of TACE inhibitors that demonstrated excellent in vitro potency against isolated TACE enzyme and excellent selectivity over MMPs 1, 2, 9, 13, and 14. (c) 2006 Elsevier Ltd. All rights reserved.